A mutagenized subline of Balb/c 3T3 cells in culture has been obtained (designated THO) which is resistant to thioguanine and ouabain, permitting isolation of cell hybrids between it and transformed cells in selected medium. The regulation of expression of transformation will be studied in cell hybrids between THO and viral, chemically, or spontaneously transformed murine cells to determine whether it is consistent with dominant or recessive patterns. If recessive, we will attempt to restore the untransformed phenotype by complementation between different transformed lines. Such an approach can be used to define prototype cell lines which are transformed at different steps. Conversely, transformants which behave in a dominant manner, including several already identified, will be used as donors in gene transfer experiments with normal human fibroblasts as recipients employing the techniques of microcell fusion and chromosome-mediated gene transfer. In this way, we will attempt to "map" genetic loci responsible for expression of transformation using chromosome banding and enzyme analyses.